crossing96/oncoscreening huggingface dataset:
PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer.	BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.	bladder
Mucinous Cystadenoma of the Urachus and Review of Current Classification of Urachal Mucinous Cystic Neoplasms.	Urachal neoplasms are uncommon and represent a minor portion of bladder tumors. According to the recently updated World Health Organization classification (2016), these tumors are classified as adenomas, adenocarcinomas, nonglandular neoplasms, and mixed carcinomas. The mucinous cystic neoplasms represent a small percentage of urachal tumors with morphologic spectrum ranging from benign mucinous cystadenoma to borderline mucinous cystic tumor of low malignant potential and to malignant mucinous cystadenocarcinoma. Benign urachal mucinous cystic adenomas are exceedingly rare, and only a few cases have been reported in the literature to date. The goal of this review is to summarize the clinical features, histopathologic characteristics, treatment, and prognosis of urachal mucinous cystadenoma in light of differentiating them from mucinous cystic tumor of low malignant potential and mucinous cystadenocarcinoma.	bladder
Long Noncoding RNA LBCS Inhibits Self-Renewal and Chemoresistance of Bladder Cancer Stem Cells through Epigenetic Silencing of SOX2.	PURPOSE: Chemoresistance and tumor relapse are the leading cause of deaths in bladder cancer patients. Bladder cancer stem cells (BCSCs) have been reported to contribute to these pathologic properties. However, the molecular mechanisms underlying their self-renewal and chemoresistance remain largely unknown. In the current study, a novel lncRNA termed Low expressed in Bladder Cancer Stem cells (lnc-LBCS) has been identified and explored in BCSCs. EXPERIMENTAL DESIGN: Firstly, we establish BCSCs model and explore the BCSCs-associated lncRNAs by transcriptome microarray. The expression and clinical features of lnc-LBCS are analyzed in three independent large-scale cohorts. The functional role and mechanism of lnc-LBCS are further investigated by gain- and loss-of-function assays in vitro and in vivo. RESULTS: Lnc-LBCS is significantly downregulated in BCSCs and cancer tissues, and correlates with tumor grade, chemotherapy response, and prognosis. Moreover, lnc-LBCS markedly inhibits self-renewal, chemoresistance, and tumor initiation of BCSCs both in vitro and in vivo. Mechanistically, lnc-LBCS directly binds to heterogeneous nuclear ribonucleoprotein K (hnRNPK) and enhancer of zeste homolog 2 (EZH2), and serves as a scaffold to induce the formation of this complex to repress SRY-box 2 (SOX2) transcription via mediating histone H3 lysine 27 tri-methylation. SOX2 is essential for self-renewal and chemoresistance of BCSCs, and correlates with the clinical severity and prognosis of bladder cancer patients. CONCLUSIONS: As a novel regulator, lnc-LBCS plays an important tumor-suppressor role in BCSCs' self-renewal and chemoresistance, contributing to weak tumorigenesis and enhanced chemosensitivity. The lnc-LBCS-hnRNPK-EZH2-SOX2 regulatory axis may represent a therapeutic target for clinical intervention in chemoresistant bladder cancer.	bladder
Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer.	PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6(+) and OV6(-) bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6(+) CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6(-) cells, OV6(+) bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6(+) CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6(+) bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.	bladder
Cell-type-specific CD73 expression is an independent prognostic factor in bladder cancer.	CD73 is an adenosine-producing cell surface enzyme, which exerts strong anti-inflammatory and migration modulating effects in many cell types. We evaluated the potential of CD73 as a biomarker in predicting the outcome of bladder carcinoma. CD73 expression in tumor and stromal cells was analyzed using immunohistochemistry in 270 bladder cancer (BC) patients [166 non-muscle-invasive BC (NMIBC) and 104 muscle-invasive BC (MIBC) tumors]. The correlations of CD73 with clinical and pathological characteristics were evaluated with Pearson's and Fischer's tests. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the association between CD73 expression and outcome. CD73 expression showed substantial variation in basal and suprabasal layers of the cancerous epithelium, stromal fibroblasts, endothelial cells and lymphocytes in different tumor specimens. In log-rank analyses, CD73 expression in cancer cells associated with better survival both in NMIBC and MIBC, whereas CD73 positivity in stromal fibroblasts associated with impaired survival in NMIBC. In multivariable models, CD73 negative epithelial cells in both BC types and CD73 negative endothelial cells in MIBC were independent factors predicting poor outcome. We conclude that in contrast to many other cancer types, high CD73 expression in BC predicts favorable prognosis.	bladder
Targeted and Untargeted Detection of DNA Adducts of Aromatic Amine Carcinogens in Human Bladder by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.	Epidemiological studies have linked aromatic amines (AAs) from tobacco smoke and some occupational exposures with bladder cancer risk. Several epidemiological studies have also reported a plausible role for structurally related heterocyclic aromatic amines present in tobacco smoke or formed in cooked meats with bladder cancer risk. DNA adduct formation is an initial biochemical event in bladder carcinogenesis. We examined paired fresh-frozen (FR) and formalin-fixed paraffin-embedded (FFPE) nontumor bladder tissues from 41 bladder cancer patients for DNA adducts of 4-aminobiphenyl (4-ABP), a bladder carcinogen present in tobacco smoke, and 2-amino-9 H-pyrido[2,3- b]indole, 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine and 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline, possible human carcinogens, which occur in tobacco smoke and cooked meats. These chemicals are present in urine of tobacco smokers or omnivores. Targeted DNA adduct measurements were done by ultra-performance liquid chromatography-electrospray ionization multistage hybrid Orbitrap MS. N-(2'-Deoxyguanosin-8-yl)-4-ABP ( N-(dG-C8)-4-ABP) was the sole adduct detected in FR and FFPE bladder tissues. Twelve subjects (29%) had N-(dG-C8)-4-ABP levels above the limit of quantification, ranging from 1.4 to 33.8 adducts per 10(9) nucleotides (nt). DNA adducts of other human AA bladder carcinogens, including 2-naphthylamine (2-NA), 2-methylaniline (2-MA), 2,6-dimethylaniline (2,6-DMA), and lipid peroxidation (LPO) adducts, were screened for in bladder tissue, by our untargeted data-independent adductomics method, termed wide-selected ion monitoring (wide-SIM)/MS(2). Wide-SIM/MS(2) successfully detected N-(dG-C8)-4-ABP, N-(2'-deoxyadenosin-8-yl)-4-ABP and the presumed hydrazo linked adduct, N-(2'-deoxyguanosin- N(2)-yl)-4-ABP, and several LPO adducts in bladder DNA. Wide-SIM/MS(2) detected multiple DNA adducts of 2-NA, 2-MA, and, 2,6-DMA, when calf thymus DNA was modified with reactive intermediates of these carcinogens. However, these AA-adducts were below the limit of detection in unspiked human bladder DNA (<1 adduct per 10(8) nt). Wide-SIM/MS(2) can screen for many types of DNA adducts formed with exogenous and endogenous electrophiles and will be employed to identify DNA adducts of other chemicals that may contribute to the etiology of bladder cancer.	bladder
Strong Expression of Cancertestis Antigens CTAG1B and MAGEA3 Is Correlated with Unfavourable Histopathological Features and MAGEA3 Is Associated with Worse Progression-Free Survival in Urothelial Bladder Cancer.	BACKGROUND: Cancer/testis antigens (CTA) are expressed in urothelial bladder cancer (UBC). Their therapeutical and prognostic relevance remains unclear. We studied the correlation of MAGEA3 and CTAG1B with histopathological factors in UBC and their prognostic value. METHODS: Retrospective analysis of 93 patients who underwent treatment for UBC was conducted. Besides clinical and histopathological parameters, the expression of MAGEA3 and CTAG1B was assessed by immunohistochemistry. RESULTS: Median follow-up was 75 months. Fifteen per cent of patients showed strong positive reaction to MAGEA3 staining. These tumours were statistically and significantly more often correlated with unfavourable World Health Organization (WHO) grading (G1: 0%, G2: 10.3%, G3: 23.4%, p = 0.048; low grade 0%, high grade 18.4%, p = 0.046 respectively). Correlation of CTAG1B with WHO grading was impressive with strong expression in no G1, 31.1% of G2 and 51.1% of G3 tumours (low grade 0%, high grade 43.4%, p = 0.001, respectively). Concomitant carcinoma in situ (Cis) was associated with strong CTAG1B expression (54.2% in concomitant Cis vs. 29% without concomitant Cis, p = 0.026). Kaplan-Meier analysis revealed statistically and significantly worse 5 years progression-free survival (PFS) associated with a strong expression of MAGEA3 (59 vs. 84%, p = 0.032). CONCLUSIONS: Strong CTA expression was correlated with unfavourable histopathological features. A strong expression of MAGEA3 was statistically and significantly associated with worse PFS across all stages of UBC.	bladder
A pyrazolopyrimidine based fluorescent probe for the detection of Cu(2+) and Ni(2+) and its application in living cells.	A fluorescent sensor L based on a pyrazolopyrimidine core simultaneously detects Cu(2+) and Ni(2+) ions by photoluminescence quenching, even in the presence of other metal cations. Sensor L possesses high association constants of 5.24 × 10(3) M(-1) and 2.85 × 10(4) M(-1) and low detection limits of 0.043 μM and 0.038 μM for Cu(2+) and Ni(2+), respectively. The binding stoichiometry ratios of L to Cu(2+) or Ni(2+) is 1:1 as determined by Benesi-Hildebrand and Job's plots, and by crystal structures. DFT calculations on L-Cu(2+) indicated reduced electron donation from the coordinated pyrazolopyridine to the fused pyrimidine and pendant phenyl group which, together with a smaller HOMO-LUMO orbital gap could favour non-radiative decay and explain the observed fluorescence quenching. Sensor L possessed low cytotoxicity and good imaging characteristics for Cu(2+) and Ni(2+) in living cells, suggesting potential applications for detecting Cu(2+) and Ni(2+)in vivo.	bladder
Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder.	The substantial difference between normal cells and cancer cells in terms of their energy metabolism in mitochondria provides an interesting basis for the development of novel therapeutic agents targeting energy machinery of tumour cells. TOMM34 is one of the Tom (translocase of the outer membrane of mitochondria) family that was found to be overexpressed in colorectal, hepatocellular, lung and early invasive breast carcinomas. The expression profile of mitochondrial translocases in bladder cancer compared to normal urinary bladder tissues has not been investigated yet. Therefore, the aim of the current study is to investigate the expression pattern of TOMM34 in bladder cancer tissues and explore its correlation with the clinico-pathological parameters of those cases. Sixty patients who underwent either transurethral resection or radical cystectomy for bladder cancer were included in this study with revision of all their clinicopathological data and tumor slides. Ten histologically normal urothelial biopsies were also included. Immunohistochemical staining for TOMM34 was done and semi-quantitatively scored using the modified H-score. All relations were analysed using established statistical methodologies. TOMM34 overexpression was significantly associated with high tumour stage, muscle invasion and high grade. Significant positive association was observed between TOMM34 expression and poor outcome in terms of shorter disease-specific survival. This study suggests TOMM34 as a biomarker of progression and poor prognosis in urothelial cell carcinoma patients. Furthermore, we suggest a role played by mitochondrial machinery in urothelial cell carcinoma progression, which is a potential target for the newly-discovered vaccine therapy for urothelial cell carcinoma.	bladder
[Risk Factors for Wound Healing of Infective Surgical Incision after Radical Cystectomy in Patients of Muscle Invasive Bladder Cancer].	OBJECTIVE: To evaluate the risk factors for wound healing of infective surgical incision in patients of muscle invasive bladder cancer undergoing radical cystectomy. METHODS: This study retrospectively collected clinical data of the patients who received radical cystectomy and experienced incisional infection after operation between January 2009 and December 2016. The patients were divided into early healing group and delayed healing group (the healing time is less or more than 14 d after operation). The risk factors for wound healing and infection were analyzed by single factor and multivariate logistic regression. RESULTS: A total of 171 patients with wound infection after radical cystectomy were included in the study. The average time of wound healing time was (17.9±16.9) d. There were 118 and 53 patients in early healing group and delay healing group respectively. Age, body mass index (BMI), operative incision type, preoperative albumin level, diabetes mellitus, infection wound size, infection wound with sinus, postoperative intestinal fistula and urinary fistula were statistically significant differences between the two groups (P<0.05).Univariate logistic regression analysis indicated that male, older than 65 yr., T(4) stage, Type-Ⅲ surgical incision (infective incision), low preoperative albumin level (<30 g/L), hemoglobin level (<90 g/L), diabetes, wound size (>30 mm), intestinal fistula, urinary fistula were risk factors for delayed wound-healing. Multivariate logistic regression analysis revealed that Type-Ⅲ surgical incision and wound size (>30 mm) were independent risk factors for delayed wound healing. CONCLUSION: Type-Ⅲ surgical incision and the size of wound (>30 mm) are independent risk factors for delayed wound healing after radical cystectomy in bladder cancer patients.	bladder
A systematic review of observational studies of the association between pioglitazone use and bladder cancer.	AIM: To conduct a systematic review of all observational studies on the effect of pioglitazone on the risk of bladder cancer. METHODS: The MEDLINE and EMBASE databases were queried for papers published between 1 January 2000 and 30 October 2017. We took into consideration observational studies (both retrospective and prospective) that included participants with Type 2 diabetes prescribed anti-hyperglycaemic drugs. RESULTS: While some studies reported an association, others did not, and meta-analyses of these studies showed a significantly increased risk; however, while meta-analysis is a powerful and practical statistical tool, its results should be considered with caution when applied to widely heterogeneous studies. We describe how many of these studies are affected by different types of bias, most notably time-related biases, which should preclude a pooled analysis that would result in biased estimation of the risk. CONCLUSIONS: Given existing data, it is not appropriate to pool the outcomes of highly heterogeneous studies and further rigorously conducted observational research is needed to clarify the role of pioglitazone use on the incidence of bladder cancer.	bladder
Lymphovascular invasion have a similar prognostic value as lymph node involvement in patients undergoing radical cystectomy with urothelial carcinoma.	To determine the prognostic value of lymphovascular invasion (LVI) in patients with bladder cancer who underwent radical cystectomy. Total of 747 patients underwent radical cystectomy; of these, only 164 did not undergo lymph node dissection (LND). The patients were divided into 4 groups: N0, N1, LVI without LND, and non-LVI without LND. Patients in the N1 and LVI groups had significantly higher T stages and grades, as well 1.5- to 2-fold higher recurrence and mortality rates. Overall survival (OS) was significantly poorer in the N1 group, compared with the N0 and non-LVI groups (p = 0.001 and 0.012), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Recurrence-free survival (RFS) was also significantly poorer in the N1 group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001), and in the LVI group relative to the N0 and non-LVI groups (p = < 0.001 and <0.001). Among patients undergoing radical cystectomy, the clinical results predicted by LVI were similar to those predicted by lymph node involvement. Therefore, the role of adjuvant chemotherapy or immunotherapy may need to be prospectively evaluated in LVI-positive patients regardless of T stage after radical cystectomy.	bladder
Melatonin protects chronic kidney disease mesenchymal stem cells against senescence via PrP(C) -dependent enhancement of the mitochondrial function.	Although mesenchymal stem cell (MSC)-based therapy is a treatment strategy for ischemic diseases associated with chronic kidney disease (CKD), MSCs of CKD patients undergo accelerated senescence, with decreased viability and proliferation upon uremic toxin exposure, inhibiting their utility as a potent stem cell source for transplantation therapy. We investigated the effects of melatonin administration in protecting against cell senescence and decreased viability induced by pathophysiological conditions near the engraftment site. MSCs harvested from CKD mouse models were treated with H(2) O(2) to induce oxidative stress. CKD-derived MSCs exhibited greater oxidative stress-induced senescence than normal-mMSCs, while melatonin protected CKD-mMSCs from H(2) O(2) and associated excessive senescence. The latter was mediated by PrP(C) -dependent mitochondrial functional enhancement; melatonin upregulated PrP(C) , which bound PINK1, thus promoting mitochondrial dynamics and metabolism. In vivo, melatonin-treated CKD-mMSCs survived longer, with increased secretion of angiogenic cytokines in ischemic disease engraftment sites. CKD-mMSCs are more susceptible to H(2) O(2) -induced senescence than normal-mMSCs, and melatonin administration protects CKD-mMSCs from excessive senescence by upregulating PrP(C) and enhancing mitochondrial function. Melatonin showed favorable therapeutic effects by successfully protecting CKD-mMSCs from related ischemic conditions, thereby enhancing angiogenesis and survival. These results elucidate the mechanism underlying senescence inhibition by melatonin in stem cell-based therapies using mouse-derived CKD-mMSCs.	bladder
Patient-Centered Outcomes in Bladder Cancer.	PURPOSE OF REVIEW: To summarize current knowledge on patient-prioritized outcomes for their bladder cancer care. RECENT FINDINGS: Patient-centered outcomes research seeks to help patients identify the right treatment for the right patient at the right time in their care. As such, patient-centered outcomes research relies on studying a treatment's impact on patient-centered outcomes. Some outcomes, like survival, are commonly prioritized by patients and by clinical experts. Patients often place greater emphasis than experts on quality of life outcomes. Thus, many patient-centered outcomes are also patient-reported outcomes. Unique domains that are often prioritized by patients, but overlooked by experts, include the costs and financial impact of care, anxiety, and depression related to a health condition, and the impact of a condition or its treatment on a caregiver or loved one. Patient-centered outcomes are realizing greater recognition for their innate importance and potential to augment the impact of research studies. Although patient-centered outcomes are often patient-reported outcomes, this is not universal. Unique to bladder cancer, the availability of a research-oriented Patient Survey Network intended to identify research questions that are important to patients may be an opportunity to broadly solicit input on patient-centered outcomes for bladder cancer research questions.	bladder